1. Technical Field
The present invention is related to nitrogen mustard analogs with arms of unequal reactivity on different nitrogen atoms. More particularly, the present invention is related to 1-(2-chloroethyl)-4-(3-chloropropyl)-piperazine, dihydrochloride or similar halo-derivatives and method of preparing the same. The new analogs are less toxic, potent, cancer chemotherapeutic agents.
2. State of the Art
Tertiary amine alkylating agents with one or two beta-haloethyl groups attached to nitrogen have been used in a variety of pharmacologic regimens. The former are employed principally as alpha adrenergic blockers and the latter, frequently described as nitrogen mustards, are cytotoxic agents. Analogs of nitrogen mustards containing a beta-haloethyl group and a gamm-halopropyl group attached to the same nitrogen have been known and reported to be effected cancer chemotherapeutic agents. Piperazine mustard, 1,4-bis(2-chloroethyl)piperazine, has also been prepared and found to be active against murine leukemia (Burchenal et al., Cancer, 4: 353, 1951), but its analog containing a beta-chloroethyl group and a gamma-chloropropyl group on different nitrogens has not been produced.